Risk Of Renal Damage From Large Dose Vitamin-D Therapy

Vit D in high dosage is a well established treatment of hypoparathyroidism (HP),pseudohypoparathyroidism (PHP), vit D dependency rickets (VDDR) and hypophosphatemic rickets (HPR). The few systematic assessments of its long-term effects on renal status have been in pts with vit D refractory rickets; some of these pts showed histological damage or functional impairment. We studied 26 pts (10 HP, 2 PHP, 6 VDDR, and 8 HPR)who received vit D or its metabolites for 1-21 (mean 11) yrs. Therapy was supervised according to a standard protocol at a special pediatric clinic, usually from the time of diagnosis. Plasma Ca was determined 2-monthly for pts on vit D or 25-OHD3 and monthly for those on 1,25-(OH)2D3. Treatment was interrupted if plasma Ca exceeded 10.5 mg/dl and resumed with 80% of the previous dose once normocalcemia returned.The pts were normocalcemic when the studies were carried out. 7/26 had diminished GFR, 5/25 concentration defect, 1/14 acidification defect. Renal histology showed tubulo-interstitial nephritis and/or calcium deposits in 17/26 pts Eight of the pts with histological abnormalities had functional impairment; however, 2 of the 9 pts with normal histology also had functional impairment. The incidence of histological abnormalities was correlated with the duration of hypercalcemia and with diagnosis, being lowest in VDDR. These studies indicate that pts receiving large dose vit D therapy are at a high risk of sustaining histological and functional damage of the kidney.